Omicron-alkyl-omicron-cycloalkyl-s-alkylthiolphosphoric acid esters



United States Patent Ofifice Patented Dec. 27, 1966 6 Claims. 61. 260-948) The present invention relates to and has as its objects new and useful insecticidally active phosphorus containing compounds. More specifically this invention is concerned with 0,0-dialkyland O-alkyl-O-cycloalkyl-S-alkylthiolphosphoric acid esters of the formula as Well as processes for the production of such compounds.

In the above mentioned formula R stands for a secondary alkyl or a c-ycloalkyl radical, R denotes a linear preferably lower alkyl radical and R denotes an optionally substituted alkyl or aralkyl radical.

In the German patent specification No. 835,145 there has already been described a process for the production of 0,0-dialkyl-thiophosphoric acid ammonium salts from symmetrical dialkyl phosphites, where sulphur is added on dialkyl phosphites in the presence of ammonia.

This reaction proceeds as follows:

By the addition of sulphur to the mentioned dialkyl phosphites the ammonium salts of 0,0-dialkyl-thionphosphoric acids (1) are intially formed in practically quantitative yields. These substances (I) are in equilibrium with the isomeric thiol form (11) Upon alkylation of the 0,0-dialkylthionophosphoric acid ammonium salts (I) there are formed 0,0-dialkyl-S-alkylrived from the compounds (II).

According to the data of the cited German patent specification such 0,0-dialkylthiophosphoric acid salts are only obtained in which the alkoxy groups are derived from primary alcohols. The same applies to other literature where likewise only compounds have previously been described in which the alkoxy groups of the above formulae are of primary character.

In accordance with the present invention it has now been found that it is also easy to produce from the nowadays readily obtainable asymmetrical dialkyl phosphites of the formula wherein R stands for a secondary alkyl or a cycloalkyl radical and R denotes a linear, preferably lower alkyl- In these formulae theradicals R and R have the above mentioned significance. The compounds of the class III, as can be seen from the formulae, stand in equilibrium with the compounds of class IV.

It has further been found that by alkylation of the ammonium salts of the type IV 0,0-dialkylor O-alkyl-O- cycloalkyl-S-alkyl-thiolphosphoric acid .esters are formed which have excellent insecticidal and, in part, also nematodicidal properties.

For the alkylation of the above mentioned 0,0-dialkyland O-alkyl-O-cycloalkylthiophosphoric acid ammonium salts those alkyl compounds are preferably used according to' the present invention which are known in the produc tion of effective insecticides based on phosphoric acid esters in which the two O-alkyl radicals are of primary character. These are in the first instance, alkylor aryl mercaptoalkyl halides, N-alkylor N,N-dialkylaminoalkyl halides, cyanalkyl halides, alkoxycarbonylalkyl halides, alkylmercaptocarbonylalkyl halides, N-alkylor N,N-dialkylaminocarbonylalkyl halides, aralkyl halides or the corresponding tosylates, and the like.

As already mentioned above the new compounds very effectively kill insects like aphids, spider mites, caterpillars, flies etc. as well as nematodes. They distinguish themselves especially by a very good contact-insecticidal activity and mostly also by a systemic and ovicidal action.

At the same time they have .an activity on eating insects such as caterpillars. Most surprisingly they are of remarkably low toxicity against mammals. For this reason the inventive products are to be used as pest control agents, especially in plant protection. They may be used in the same manned as other known phosphoric insecticides, i.e. ina concentration from about 0.00001% to about 1% diluted or extended with suitable solid or liquid carriers or diluents. Examples of such solid carriers are talc, chalk, bentonite, clay and the like, as liquid carriers there may be mentioned water (if necessary with commercial emulsifiers), alcohols, especially lower alcohols such as methanol or ethanol, ketones, especially lower ketones such as acetone or methly ethyl ketone, liquid hydrocarbons and the like. The new compounds may furthermore be used in combination with each other or with known insecticides, fertilizers etc.

As examples for the special utility the inventive compounds of the following formulae have been tested against aphids (compounds I and II), spider mites (compounds I, H and III) and caterpillars (compounds I, II and III). Aqueous dilutions of these compounds have been prepared by mixing the active ingredient-s with the same amounts of dimethyl formamide as an auxiliary solvent adding thereto 20% by weight referred to active ingredient of a commercial emulsifier consisting of a benzyl hydroxy polyglycol ether containing about to glycol ethers, and diluting this premixture at last with water to the desired concentration indicated in the following paragraphs:

The tests have been carried out as follows:

(a) Against aphids (species Doralis fabae): heavily infested bean plants (Vicia faba) have been sprayed drip wet with solutions as prepared above. The effect has been determined after 24 hours by counting the dead pests either on the surface of the soil or still remaining on the plants. The following results have been obtained:

Compound aqueous concentration (in percent active ingredient] water Killing rate (in percent) Evaluation has been carried out after 24 hours, 48 hours and 8 days. The following results have been obtained:

Compound aqueous conceutration (in percent Killing rate (in percent) active ingredient/water) ovicidal action. 0 001 40 ovieidal action. 0 0001 Compound aqueous concentration (in percent Killing rate (in percent) active ingredient/water) The following examples are given for the purpose to illustrating the invention.

Example 1 (a) sec. 041100 8 see. G4H O\fi P-ONH4 2 r-s-nn;

CHaO CHQO 152 g. (1 mol) of O-methyl-O-sec.-butylphosphite (B.P. 68 C./ 2 mm. Hg) are dissolved in 200 cc. of methanol. To this solution there are added 32 g. of finely powdered sulphur, and anhydrous ammonia is introduced with stirring at an internal temperature of 30 to 40 C. until the sulphur is completely dissolved. The solvent is subsequently evaporated. There remain g. (52% of the theoretical yield) of the O-methyl-O-sec.-butyl-thiophosphoric acid ammonium salt which is suificiently pure for further reactions.

In an analogous manner as already described above there is obtained from Omethyl-O-isopropyl-phosphite by the reaction with sulphur and ammonia the corresponding O-methyl-O-isopropyl-thiophosphoric acid ammonium salt. The yield amounts to 60% of the theoretical.

61 g. (0.3 mol) of O-methyl-O-sec.-butyl-thiophosphoric acid ammonium salt are dissolved in 200 cc. of acetonitrile. 37 g. of fi-ethylmercaptoethyl chloride are added to this solution at 75 to 80 C. with stirring. Stirring is continued at 80 C. for a further hour, and the reaction product then poured into 300 cc. of ice water. The separated oil is taken up in 200 cc. of benzene. The benzene solution is washed with water and subsequently dried with sodium sulphate. Upon fractionation there are obtained 64 g. (79% of the theoretical yield) of the O-methyl O sec. butyl S (6 ethyl mercaptoethyl) thiolphosphoric acid ester of -B.P. 94 C./ 0.01 mm. Hg. The product is a colourless water-insoluble oil.

Spider mites are killed to 90% by 0.001% solutions and aphids are destroyed to 50% even by 0.0001% solutions of the ester. Moreover the compound shows an ovicidal activity against the eggs of spider mites.

Example 2 80 g. (0.4 mol) of O-methyl-O-sec.-butyl-thiophosphoric acid ammonium salt are dissolved in 250 cc. of acetonitrile. g. of chloromethyl thioethyl ether are added to this solution at to C. with stirring. Stirring is continued at the indicated temperature for one hour, and the reaction mixture is then worked up as described in Example 112. 72 g. (71% of the theoretical yield) of the O-methyl-O-sec.-butyl-S-(ethyl-mercap tomethyl)-thiolphosphoric acid ester of B.P. 81 C./0.01 mm. Hg are thus obtained.

The compound is a colourless water-insoluble oil.

Aphids and spider mites are completely destroyed by 0.001% solutions, caterpillers by 0.01% solutions of 6 yield) of the O-methyl-O-pinacolyl-thiophosphoric acid ammonium salt remain.

92 g. (0.4 mol) of O-methyl-O-pinacolyl-thiophosphoric acid ammonium salt are dissolved in 250 cc. of acetonitrile. 50 g. of fi-ethylmercapto-ethyl chloride are added to this solution at C. with stirring. The temperature of the mixture is maintained at 80 C. for one hour and the product then worked up as described in Example 1b. 94 g. (78% of the theoretical yield) of the O methyl O pinacolyl S (,8 ethylmercaptoethyl)- thiolphosphoric acid ester of B.P. 98 C./0.01 mm. Hg are thus obtained.

Spider mites are completely destroyed by 0.01% solutions of the ester. The systemic action of 0.1% solutions of the compound against aphids is Moreover the product possesses an ovicidal activity against the eggs of spider mites.

Exam le 4 the ester, ticks are killed to 80% by 0.005% solutions. p Moreover the compound shows an ovicidal activity (grim-0 0 0011 against spider mites. }L

Under similar reaction conditions, the following com- 30 pounds are obtained: CH3

Insecticidal properties Yield (per- Structure cent of the theoretical) Concentra- Killingrate Physical properties Administration against tion of active of pests in substance percent sec. 04H0O O 1 -CN 57 B P 93 C /0 01mm H {Caterpillars 1001 80 2 Mosquito larvae 0.0001 100 CH3O see. C4H9O\(") /P--SCH2SC1 5 Not distillable Oil {g g fg 8'8} 33 CHaO see. C4HQO\(|;|)

Aphids- 0.1 100 /P S CH2 63 {Spider mites 0.1 100 CHKO sec. OiH9O\(") n Aphids (systemic action) 0.1 100 P s CH2 00 NH CH3 44 gg gig g gs Water {Caterpillars 0.01 80 CH3O S80. C4H9O 0 Aphids (contactnscc- 0.001 100 PSCHQCHz-CN 44 B-P-,98 C./0.01mm.Hg ticidal action).

Aphids (systemic action).. 0.1 100 OHaO Example 3 g. (0.5 mol) of O-methyl-O-pinacolyl-thiophosphoric acid ammonium salt are dissolved in 250 cc. of (a) CH CH3 acetonitrile. 56 g. of chloromethyl-thioethyl ether are g. (1 mol) of O-methyl-O-pinacolyl phosphite 70 added to this solution at 50 to 60 C. with stirring. Subsequently the mixture is heated at 70 C. for a further hour and then worked up as described in Example 1b. 94 g. (65% of the theoretical yield) of the O-methyl-O- pinacolyl-S-(ethyl-mercaptomethyl)-thiolphosphoric acid ester of B.P. 96 C./0.01 mm. Hg are thus obtained.

Aphids are killed to 90% and spider mites to 100% by 0.01% solutions of the ester. Moreover the compound shows an ovicidal activity against the eggs of distilling off the solvent, 126 g. (55% of the theoretical 75 spider mites.

In a similar manner the following compounds are obtained:

8 114 g. (0.5 mol) of O-methyl O-cyclohexyl-thiophosphoric acid ammonium salt are dissolved in 250 cc. of

Y d Insecticidal properties e Structure percent I of the Goncentra- Killin theore tion of rate tical Physical properties Administration against active subpests in stance in percent percent (CHs)a-C O OCH:

95 {Not distillable, water- {Spider mites 0. 01 100 insoluble oil. Mosquito larvae O. 001 100 on. S-CHzS-@-Ol a)aC\ (fi/O CH3 Aphids contaot-insec- 0.01 100 OHOP 55 g gig fil g ig ticidal action). O H S CH CO NH OH Aphids (systemic action) 0.1 100 (CH3)3C 0 00113 OH--OP 66 Not distillible, water- Aphids- 0. 1 100 g insoluble oil. 0 a SOH Cl (CH3)3C\ g/OCH:

--{5.5 3212156533111:::::: 8: iii C 3 S-CHr-CHz-CN (CH3)3U\ (fi/OCHa Spider mites 0.01 100 0 P 57 Aphids (systemicaction) 0.1 100 CH3 S-CHa-CN Example acetonitrile. To this solution 63 g. of fi-ethylmercapto- (a) ethyl chloride are added at 80 C. with stirring. The reaction mixture is stirred at 80 C. for a further hour and s 00H, 0 00H H/ H/ then worked up as described in Example 1b. 115 g. H (77% of the theoretical yield) of the O-methyl-O-cyclo- 178 g. (1 mol) of O-methyl-O-cyclohexyl phosphite (B.P. 124 C./7 mm. Hg) are dissolved in 200 cc. of methanol. 32 g. of sulphur are added to the solution with stirring. Anhydrous ammonia is subsequently introduced into the mixture at 40 to C. until the sulphur is dissolved. The solvent is then distilled oil in a vacuum. 150 g. (66% of the theoretical yield) of the O-methyl-O-cyclohexyl-thiophosphoric acid ammonium salt are obtained.

114 g. (0.5 mol) of O-methyl-O-cyclohexyl-thiophosphoric acid ammonium salt are dissolved in 250 cc. of acetonitrile. Subsequently 38 g. of chloracetonitrile are added to this solution at 65 to 70 C. with stirring. The reaction mixture is then heated at 80 C. for 1 hour and Worked up as described in Example 1b. 70 g. (56% of the theoretical yield) of the O-methyl-O-cyclohexyl-S- (cyanomethyl)-thiolphosphoric acid ester of B.P. 104 C./0.01 mm. Hg are thus obtained.

Aphids are killed to 90% and caterpillars are completely destroyed by 0.01% solutions of the compound. Spider mites are killed to 40% by 0.001% solutions of the ester. Moreover the product shows an ovicidal activity against the eggs of the last mentioned pests.

Example 6 OCH;

hexyl-S-(B-et-hylmercaptoethyl)-thiolphosphoric acid ester are thus formed of B.P. 112 C./0.01 mm. Hg.

Aphids and spider mites are killed to by 0.001% solutions of the ester.

Example 7 114 g. (0.5 mol) of O-methyl-O-cyclohexyl-thiophos phoric acid ammonium salt are dissolved in 250 cc. of acetonitrile. 67 g. of fl-chloropropionitrile are added to the solution at 80 C. with stirring. Subsequently the mixture is stirred at 80 C. for a further 2 hours and then worked up as described in Example 1b. 56 g. of O-methyl-O-cyclohexyl-S-(fi-cyanethyl) thiolphosphoric acid ester of B.P. 108 C./ 0.01 mm. Hg are thus obtained.

Aphids are completely destroyed by 0.1% solutions of the ester. The systemic action of 0.1% solutions against aphids is Example 8 114 g. (0.5 mol) of O-methyl-O-cyclohexyl-thiophosphoric acid ammonium salt are dissolved in 250 cc. of acctonitrile. 56 g. of chloromethyl-thioethyl ether are added to this solution at 50 to 60 C. With stirring. The temperature of the reaction mixture is maintained at 60 C. for 1 hour and the mixture is then worked up as described in Example 115. 74 g. (52% of the theoretical yield) of the O-methyl-O-cyclohexyl-S-(ethylmercapto- 9 methyD-thiolphosphoric acid ester of B.P. 106 C/0.01 mm. Hg are thus obtained.

Spider mites are completely destroyed by 0.01% solutions of the compound and caterpillars are killed to 40% even by 0.001% solutions. Moreover the ester shows an ovicidal activity against the eggs of spider mites.

Example 9 94 g. (0.5 mol) of O-methyl-O-isopropylthiophosphoric acid ammonium salt are slurried in 250 cc. of acetonitrile and 36 g. (0.5 mol) of chloroacetonitrile are added with stirring at 50 to 60 C. to this slurry. Subsequently the reaction mixture is stirred for 3 hours at 60 C. and then poured into 300 cc. of ice-water and the separated oil is absorbed in 300 cc. of benzene. The benzene solution is washed with water and then dried over sodium sulphate. After distilling off the solvent there are obtained 75 g. (67% of the theoretical yield) of the O-met'hyl-O-isopropyl-S-(cyanomethyl)-thiolphosphoric acid ester as a colourless water-insoluble oil of the refractive index n =1.4474. The mean toxicity of the compound (LD on rats per os amounts to 5 mg. per kg. of animal.

Aphids are completely destroyed by 0.01% solutions of the ester; spider mites are killed to 50% even by 0.001% solutions.

Example sHrO O 94 g. (0.5 mol) of O-methyl-O-isopropyl-thiophosphoric acid ammonium salt are slurried in 250 cc. of acetonitrile. To this slurry there are added 67 g. (0.5 mol) of B-chloropropionitrile with strong stirring at 75 C. Subsequently the reaction mixture is stirred for 3 hours at 75 to 80% C. and then poured into 300 cc. of ice-Water. The separated oil is absorbed in 300 cc. of benzene. The benzene solution is Washed with water and dried over sodium sulphate. After distilling off the solvent there are obtained 62 g. (52% of the theoretical yield) of O-methyl-O-isopropyl-S-(ti-cyanoethyl)-thiolphosphoric acid ester as colourless water-insoluble oil of the refractive index n- =1.4787. The mean toxicity of the compound (LD on rats per os amounts to 50 mg. per kg. of animal. Mosquito larvae are completely destroyed by 0.001% solutions of the ester. The systemic action of 01% solutions against aphids is 100%.

Example 11 CH O To a solution of 94 g. (0.5 mol) of O-methyl-O-isopropyl-thiophosphoric acid ammonium salt in 300 cc. of acetonitrile there are added at 70 C. 54 g. (0.5 mol) of chloro acetic .acid-N-methyl-amide, dissolved in 50 cc. of acetonitrile, the reaction mixture is stirred for 2 hours at the stated temperature and then poured into 400 cc. of ice-water. The separated oil is absorbed in 300 cc. of chloroform and the solution in chloroform dried over sodium sulphate. Subsequently the solvent is removed by distillation. A residue of 71 g. (59% of the theoretical yield) of O-methyl-O-isopropyl-S-(N-methyl-carbaminyl-methyl-)-thiolphospboric acid ester as a viscous, water-insoluble oil is obtained.

, Analysis.Calculated for a molecular Weight of 241: N, 5.8%; S, 13.3%; P, 12.9%. Found: N, 5.5%; S, 14.6%; P, 12.9%.

The mean toxicity of the compound (LD on rats per os amounts to 10 mg. per kg. of animal.

10 The systemic action of 0.004% solutions of the ester is 100% Example 12 In an analogous manner as described inthe aforementioned Examples there is obtained from 114 g. (0.5 mol) of O-methyl-O-cyclohexylthiophosphoric acid ammonium salt by the reaction with 54 g. of chloro acetic acid-N- methylamide the -O-methyl-O-cyclohexyl-S-(N-methylcarbaminyl-methyl-)-thiolphosphoric acid ester as a lightyellow, viscous, Water-soluble oil.

The yield amounts to 97 g. (59% of the theoretical).

Analysic-C-alculated for a molecular weight of 281: N, 4.9%; S, 11.4%; P, 11.0%. Found: N, 4.9%; S, 11.5%; P, 11.2%.

The mean toxicity of the compound (LD on rats per os amount to 50 mg. per kg. of animal.

Aphids are completely destroyed by 0.01% solutions of the ester and spider mites are killed to 70% even by 0.001% solutions.

57 g. (0.3 mol) of O-methyl-O-isopropyl-thiophosphoric acid ammonium salt are dissolved in 200 cc. of acetonitrile. added to this solution with stirring at 75 C. Subsequently the reaction mixture is heated for 1 hour to C. and then poured into 300 cc. of ice-water. The sepa rated oil is absorbed in 300 cc. of benzene, the benzene solution washed with water until the neutral reaction is effected and the organic phase dried over sodium sulphate. After evaporation of the solvent there is obtained by the subsequent fractional distillation the O-methyl-O-isopropyl S (B-ethylmercapt-oethyl)-thiophosphoric acid ester as a colourless. water insoluble oil of B.P. 76 C. 0.01 mm. Hg.

The yield amounts to 64 g. (78% of the theoretical). The mean toxicity of the compound (LD on rats per os amounts to 5 mg. per kg. of animal.

Spider mites are killed to 80% by 0.00016% solutions of the ester. The systemic action of 0.00016% solutions against aphids is Example 14 iC H7O\(|? PS-CH2SCzH orno Under analogous reaction conditions as described in the aforementioned example there are obtained from 94 g. (0.5 mol) of O-methyl-O-isopropylthiophosphoric acid ammonium salt and 56 g. (0.5 mol) of chloro-methylthioethylether 67 g. (55% of the theoretical yield) of O-methyl O isopropyl-S-(-ethylmercapto-methyl)-thiolphosphoric acid ester as a Water insoluble colourless oil of B.P. 74 C./0.01 mm. Hg and the refractive index 12 1.4968. Caterpillars are completely destroyed by 0.01% solutions and spider mites are killed to 80% even 'by 0.0001% solutions of the ester.

Example 15 SCH5 10,1170 0 I 38 g. (0.5 mol) of ,8-chloroethylthioethylether are 94 g. (0.5 mol) of O-methyl-O-isopropyl-thiophosphoric acid ammonium salt are dissolved in 300 cc. of acetonitrile. 95 g. of 2-methylrnercapto-S-methyl-benzyl-chloride are added with stirring to this solution at 75 C. Subsequently the reaction mixture is stirred for 2 hours at 80 C. and Worked up as mentioned in the aforesaid example. In this way there are obtained 122 g. (76% of the theoretical yield) of O-methyl-O-isopropyl-S-(2- rnethylmercapto 5 methyl-benzyl)thiolphosphoric acid ester as a colourless, water insoluble oil.

Analysis-Calculated for a molecular weight of 320: S, 20.0%; P, 9.7%. Found: S, 20.9%; P, 9.1%.

Then mean toxicity of the compound (LD on rats per os amounts to 100 mg. per kg. of animal.

Spider mites are completely destroyed by 0.01% solutions of the ester; moreover the compound shows an ovicidal activity against the eggs of the mentioned pests.

Example 16 CHaO On rats per os the compound possesses a mean toxicity (LD of 250 mg. per kg. of animal.

Spider mites are completely destroyed by 0.01% solutions of the ester. Moreover the compound shows an ovicidal activity against the eggs of these pests.

I claim:

1. A compound of the formula RO\(II|) PSR2 wherein R stands for cyclohexyl, R stands for lower alkyl having up to 4 carbon atoms and R stands for a member selected from the group consisting of lower alkyl mercapto substituted lower alkyl, phenyl substituted lower alkyl, chlorophenyl substituted lower alkyl, lower alkyl mercapto phenyl substituted lower alkyl, lower alkyl and lower alkyl mercapto-phenyl substituted lower alkyl, phen- 5 ylmercapto substituted lower alkyl and chloro phenyl mercapto substituted lower alkyl, lower alkyl in each case having up to 4 carbon atoms.

2. A compound of the formula ROO for

2-)nz Where i1 stands for 1 or 2.

5. The compound of the following formula sonr omso2m 6. The compound of the following formula References Cited by the Examiner UNITED STATES PATENTS 1/ 1950 Cassaday et al. 260943 1/ 1950 Cassaday et al. 260943 5/ 1952 Schrader 260-461.112

5/1960 Lorenz et al 260461.112 2/1962 Chupp 260461 CHARLES E. PARKER, Primary Examiner.

IRVING MARCUS, F. M. SIRORA, R. L. RAYMOND, 50 Examiners. 

1. A COMPOUND OF THE FORMULA 